Bonnie F. Sloane, Ph.D.
Dr. Sloane's laboratory has a longstanding interest in the roles of proteolytic pathways in development and progression of cancer with an emphasis on the progression of premalignant breast disease to invasive carcinomas. Her research group has established a role for lysosomal proteases, primarily the cysteine protease cathepsin B, and the endogenous inhibitors of cysteine cathepsins (the cystatins and stefins) in malignant progression. They were the first group to uncover molecular mechanisms for the increased expression of cathepsin B in human tumors and to identify binding partners responsible for alterations in localization of cathepsin B in tumors. This includes the association of cathepsin B with caveolae on the cell surface via the direct binding of procathepsin B to S100A10, p11 or the light chain of the annexin II heterotetramer, in complex with the heavy chain annexin II.
The Sloane group has been a leader in applying live-cell imaging to proteases in order to exploit the potential of proteases as biomarkers, therapeutic targets or surrogate endpoints. For this purpose, they have established new assays to follow proteolysis by live human breast cells in real time as they form 3D structures in matrices and migrate through the matrices, thus analyzing proteolysis in 4D (3D + time). They have employed these assays to follow the interactions among breast tumor cells and tumor-associated cells in an effort to determine: 1) whether the various cellular components comprising a tumor use proteolysis to perform their functions (e.g., is there proteolysis associated with infiltration of fibroblasts and macrophages into tumors? with endothelial cell migration and formation of neovessels?); 2) the contributions of the non-cellular components of the tumor microenvironment (e.g., acidic pH and hypoxia) to tumor proteolysis and invasion; and 3) the contributions of cell:cell interactions to tumor proteolysis and invasion? In collaboration with Dr. Mattingly, they are analyzing how kinase pathways and cytokine pathways intersect with and regulate proteolytic pathways. The goal is to identify mechanisms by which the tumor microenvironment alters proteolysis in order to design and test therapeutic strategies targeting interactions between the tumor and its microenvironment. In collaboration with Dr. Xu of the College of Engineering, they are designing microfluidic platforms to grow the 3D/4D cultures and perform high content analysis for drug screening.
Current Lab Personnel
• Kingsley Osuala, Ph.D.
• Kyungmin Ji, Ph.D.
• Neha Aggarwal (Ph.D. candidate in Physiology)
• Mansoureh Sameni
• Research Assistants
• Anita Chalasani
Some Lab Alumni
• Mamoun Ahram, Ph.D. (Ph.D. in Cancer Biology 1999), Assistant Professor, University of Jordan, Amman, Jordan.
• Dora Cavallo-Medved, Ph.D. (Postdoc 2000-04), Assistant Professor of Biological Sciences, University of Windsor, Ontario, Canada
• Michael Emmert-Buck, M.D.-Ph.D. (Ph.D. in Pharmacology 1989), Head, Pathogenetics Unit, Laboratory of Pathology and Urologic Oncology Branch, National Cancer Institute, Bethesda, MD
• Christopher Jedeszko, Ph.D. (Ph.D. in Pharmacology 2009), Research Associate, Xagenic Inc., Toronto, Canada
• Jennifer Koblinski, Ph.D. (Ph.D. in Cancer Biology 1999), Assistant Professor of Pathology, Virginia Commonwealth University, Richmond, VA
• Tamara Turnsek Lah, Ph.D. (Postdoc 1985-87), Director, National Institute of Biology, Ljubljana, Slovenia
• Mona Mostafa Mohamed, Ph.D. (Avon/American Association for Cancer Research International Fellow 2005-07), Professor of Cellular and Molecular Biology, Cairo University, Cairo, Egypt - more...
• Stephanie Roshy Mullins, Ph.D. (Ph.D. in Cancer Biology 2005), Research Scientist MedImmune, Cambridge, England
• Izabela Podgorski, Ph.D. (Postdoc 2002-07), Assistant Professor of Pharmacology, Wayne State University, Detroit, MI
• Ravi Shridhar, M.D.-Ph.D. (Ph.D. in Pharmacology 2001), Assistant Member, Department of Radiation Oncology, Moffitt Cancer Center, Tampa, FL
• Bernadette Palazzalo Victor, Ph.D. (Ph.D. in Cancer Biology 2011), Postdoctoral Fellow with D. Green, St. Jude's, Memphis, TN
• David Gorski, M.D.-Ph.D., Department of Surgery, Wayne State University, Detroit, MI
• Carrie Graveel, Ph.D., Van Andel Research Institute, Grand Rapids, MI
• Lawrence Lum, M.D., D.Sc., Department of Oncology, Wayne State University, Detroit, MI
• Raymond Mattingly, Ph.D., Department of Pharmacology, Wayne State University, Detroit, MI
• Mona Mostafa Mohamed, Ph.D., Cairo University, Cairo, Egypt [more]
• Belinda Parker, Ph.D., La Trobe University, Melbourne, Australia
• Yong Xu, Ph.D., Department of Electrical and Computer Engineering, Wayne State University, Detroit, MI
Selected Recent Publications
• Estrella, V., Chen, T., Lloyd, M., Wojtkowiak, J., Cornell, H.H., Ibrahim-Hashim, A., Bailey, K., Balagurunathan, Y., Rothberg, J.M., Sloane, B.F., Johnson, J., Gatenby, R.A. and Gillies, R.J.: Acidity generated by the tumor microenvironment drives local invasion. Cancer Res. 73: 1524-1535, 2013. Published online 1/03/2013; cover image.
• Bengsch, F., Buck, A., Gunther, S.C., Seiz, J.R., Tacke, M., Pfeifer, D., von Elverfeldt, D., Sevenich, L., Hillebrand, L.E., Kern, U., Sameni, M., Peters, C., Sloane, B.F. and Reinheckel, T.: Cell type-dependent pathogenic functions of overexpressed human cathepsin B in murine breast cancer progression. Oncogene DOI: 10.1038/onc.2013.395, 2013. Published online 9/30/2013.
• Rothberg, J.M., Bailey, K.M., Wojtkowiak, J.W., Ben-Nun, Y., Bogyo, M., Weber, E., Moin, K., Blum, G., Mattingly, R.R., Gillies, R.J. and Sloane, B.F.: Acid-mediated tumor proteolysis: contribution of cysteine cathepsins. Neoplasia 15: 1125-1137, 2013; cover image.
• Kaur, H., Mao, S., Shah, S., Gorski, D.H., Krawetz, S.A., Sloane, B.F. and Mattingly, R.R.: Next-generation sequencing: a powerful tool for the discovery of molecular markers in breast ductal carcinoma in situ. Expert Rev. Mol. Diagnosis 13: 151-165, 2013.
• Aggarwal, N. and Sloane, B.F.: Cathepsin B: multiple roles in cancer. Proteomics - Clinical Applications (Special Issue on Proteases and Disease; Findeisen/Schilling, eds.), in press.
• Sloane, B.F., List, K., Fingleton, B. and Matrisian, L.: Proteases in cancer – significance for invasion and metastasis. In: Proteases – Structure and Function. Brix, K. and Stoecker, W., eds. (Springer-Verlag, New York), in press.